Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28098 | 84517;84518;84519 | chr2:178561840;178561839;178561838 | chr2:179426567;179426566;179426565 |
| N2AB | 26457 | 79594;79595;79596 | chr2:178561840;178561839;178561838 | chr2:179426567;179426566;179426565 |
| N2A | 25530 | 76813;76814;76815 | chr2:178561840;178561839;178561838 | chr2:179426567;179426566;179426565 |
| N2B | 19033 | 57322;57323;57324 | chr2:178561840;178561839;178561838 | chr2:179426567;179426566;179426565 |
| Novex-1 | 19158 | 57697;57698;57699 | chr2:178561840;178561839;178561838 | chr2:179426567;179426566;179426565 |
| Novex-2 | 19225 | 57898;57899;57900 | chr2:178561840;178561839;178561838 | chr2:179426567;179426566;179426565 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs746141297  |
-0.049 | 0.989 | D | 0.55 | 0.396 | 0.453679287548 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| T/I | rs746141297 |
-0.049 | 0.989 | D | 0.55 | 0.396 | 0.453679287548 | gnomAD-4.0.0 | 6.84296E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99502E-07 | 0 | 0 |
| T/N | rs746141297 |
0.247 | 0.957 | N | 0.496 | 0.252 | 0.295974979623 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/N | rs746141297 |
0.247 | 0.957 | N | 0.496 | 0.252 | 0.295974979623 | gnomAD-4.0.0 | 1.36859E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.319E-05 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0749 | likely_benign | 0.0686 | benign | -0.198 | Destabilizing | 0.726 | D | 0.454 | neutral | N | 0.487985323 | None | None | N |
| T/C | 0.4532 | ambiguous | 0.4168 | ambiguous | -0.27 | Destabilizing | 0.999 | D | 0.577 | neutral | None | None | None | None | N |
| T/D | 0.3156 | likely_benign | 0.2429 | benign | 0.006 | Stabilizing | 0.983 | D | 0.501 | neutral | None | None | None | None | N |
| T/E | 0.3573 | ambiguous | 0.274 | benign | -0.093 | Destabilizing | 0.983 | D | 0.48 | neutral | None | None | None | None | N |
| T/F | 0.3226 | likely_benign | 0.2607 | benign | -0.864 | Destabilizing | 0.992 | D | 0.613 | neutral | None | None | None | None | N |
| T/G | 0.1501 | likely_benign | 0.1375 | benign | -0.247 | Destabilizing | 0.895 | D | 0.447 | neutral | None | None | None | None | N |
| T/H | 0.2597 | likely_benign | 0.2186 | benign | -0.464 | Destabilizing | 0.998 | D | 0.611 | neutral | None | None | None | None | N |
| T/I | 0.2765 | likely_benign | 0.2045 | benign | -0.188 | Destabilizing | 0.989 | D | 0.55 | neutral | D | 0.525042202 | None | None | N |
| T/K | 0.2688 | likely_benign | 0.1987 | benign | -0.222 | Destabilizing | 0.968 | D | 0.498 | neutral | None | None | None | None | N |
| T/L | 0.1303 | likely_benign | 0.1115 | benign | -0.188 | Destabilizing | 0.944 | D | 0.462 | neutral | None | None | None | None | N |
| T/M | 0.1221 | likely_benign | 0.1082 | benign | -0.072 | Destabilizing | 0.999 | D | 0.579 | neutral | None | None | None | None | N |
| T/N | 0.1056 | likely_benign | 0.0916 | benign | -0.003 | Destabilizing | 0.957 | D | 0.496 | neutral | N | 0.439439228 | None | None | N |
| T/P | 0.224 | likely_benign | 0.1701 | benign | -0.168 | Destabilizing | 0.989 | D | 0.543 | neutral | N | 0.512747695 | None | None | N |
| T/Q | 0.2552 | likely_benign | 0.2093 | benign | -0.248 | Destabilizing | 0.983 | D | 0.548 | neutral | None | None | None | None | N |
| T/R | 0.2098 | likely_benign | 0.1625 | benign | 0.055 | Stabilizing | 0.983 | D | 0.531 | neutral | None | None | None | None | N |
| T/S | 0.0796 | likely_benign | 0.0771 | benign | -0.173 | Destabilizing | 0.146 | N | 0.315 | neutral | N | 0.418085308 | None | None | N |
| T/V | 0.1991 | likely_benign | 0.1547 | benign | -0.168 | Destabilizing | 0.944 | D | 0.462 | neutral | None | None | None | None | N |
| T/W | 0.6854 | likely_pathogenic | 0.6101 | pathogenic | -0.925 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | N |
| T/Y | 0.3445 | ambiguous | 0.2889 | benign | -0.611 | Destabilizing | 0.997 | D | 0.617 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.